SCLC cell lines, unlike NSCLC lines, have markedly decreased or absent class I major histocompatibility antigens. To examine whether this is a valid in vivo we have studied serial paraffin - embedded tissue sections from 36 SCLC patients and 79 NSCLC patients for expression of B2-microglobulin. Most of the tissues were completely negative or weakly positive. The opposite was true for NSCL. Thus B2-microglobulin can be used as a diagnostic marker for SCLC vs. NCLC on tissue sections. Furthermore, we demonstrated in vivo induction of B2-microglobulin on SCLC patients and mid gut carcinoid patients treated with interferon. Before interferon treatment, biopsies from 3 SCLC patients and 6 mid-gut carcinoid patients did not express B2-microglobulin. In contrast, biopsies from the same patients after interferon therapy showed clear positivity for B2-microglobulin. Lack of B2-microglobulin expression on SCLC cells may play a role in their widely metastatic behaviour, and present the patient's immune surveillance system from inhibiting their growth. In addition, our findings suggest a new novel method by which interferon exerts its antitumor effects.